A Prospective Observational Study on Multiplate®-, ROTEM®- and Thrombin Generation Examinations Before and Early After Implantation of a Left Ventricular Assist Device (LVAD)

Abstract

BackgroundHeart failure patients are frequently on coagulation-active medications before LVAD implantation and perioperative bleeding is a frequent complication after left ventricular assist device (LVAD) implantation. The role of point-of-care coagulation tests in assessing bleeding risk for LVAD implantation and the early postoperative time course of these tests is not well established.MethodsWe prospectively enrolled 25 patients with terminal heart failure undergoing LVAD implantation. Study related TRAP-, ASPI- and ADP- tests of Multiplate® platelet aggregometry, ROTEM® rotational thromboelastometry (INTEM, EXTEM, FIBTEM), thrombin generation assay and conventional laboratory studies were measured at 11 predefined time-points during the first 21 postoperative days. We examined if preoperative TRAP-, ASPI-, ADP- and ROTEM values are correlated with estimated total blood loss (primary outcome parameter) during the first 21 days after LVAD implantation and compared the baseline values of these measurements between patients with a bleeding event to those without. We performed Spearman's correlation and non-parametric tests for paired and non-paired comparisons.Results7 out of 25 (28%) patients experienced a bleeding event of which 4 required surgical revision. Of the preoperatively performed measurements the TRAP test [Spearman's Rho (ρ) = −0.5, p = 0.01], INTEM CFT (ρ = 0.72, p < 0.001), INTEM alpha (−0.7, p < 0.001), EXTEM MCF (ρ = −0.63; p < 0.001), EXTEM alpha (ρ = −0.67; p < 0.001), FIBTEM MCF (ρ = −0.41; p = 0.042), Fibrinogen (Clauss) (ρ = −0.5; p = 0.011), Anti-thrombin activity (ρ = −0.49; p = 0.013) and platelet count (ρ = −0.42; p = 0.034) were significantly correlated to total blood loss. Patients undergoing a surgical bleeding revision had significantly reduced values in TRAP—[31.5 IQR (17.25–43.5U) vs. 69 IQR (52.5–87U); p = 0.004], ASPI—[16.5 IQR (5.5–35.7U) vs. 39 IQR (24.5–62.5U); p = 0.038], ADP—[30 IQR (22–69U) vs. 12.5 IQR (8.7–21.5U); p = 0.01], EXTEM MCF—[63 IQR (57.7–63.7) vs. 67 IQR (65–75.5); p = 0.019] and EXTEM alpha [74 IQR (68.75–74) vs. 79 IQR (78–80.5); p = 0.002] values before LVAD implantation.ConclusionMultiplate® and ROTEM® measurements before LVAD implantation may identify LVAD candidates with platelet dysfunction and alterations of the primary hemostasis and could guide anesthetists and intensive care practitioners in bleeding risk stratification and in the perioperative clinical management.

Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function

“…It was shown that the severity of acquired platelet defects, i.e., reduced GPIbα and GPVI expression and reduced α IIb β 3 activation, is predictive of non-surgical bleeding events in CTD recipients, having even higher predictive power than vWF degradation parameters [ 37 ]. Further, device-implanted patients with increased bleeding risk demonstrate decreased platelet aggregation response, underscoring the importance of these acquired defects as drivers of device-related bleeding coagulopathy [ 68 ].…”

Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function

“…80 It was also reported that device-implanted patients with increased bleeding risk demonstrate decreased platelet aggregation response to biochemical agonists (ADP, TRAP-6, and arachidonic acid), underscoring the importance of these acquired defects as drivers of device-related bleeding coagulopathy. 138…”

“…80 It was also reported that deviceimplanted patients with increased bleeding risk demonstrate decreased platelet aggregation response to biochemical agonists (ADP, TRAP-6, and arachidonic acid), underscoring the importance of these acquired defects as drivers of device-related bleeding coagulopathy. 138 Routine flow cytometry used to capture and characterize shear-mediated PDMPs is known to underestimate the small-size microparticle population (<300 nm) and exosomes (<100 nm). Therefore, the number of shear-ejected microvesicles detected in our study might also be underestimated.…”

The endogenous thrombin potential in patients with left ventricular assist device or heart transplant

“…The impact of LVAD implantation on patients’ plasmatic coagulation system is challenging to investigate due to additional altering factors, particularly surgery itself and required anticoagulation ( 23 ). Thrombin generation before and after LVAD implantation has been examined in a recent study ( 24 ). However, the authors focused on longitudinal progression and did not antagonize heparinized samples.…”